389 - Identification of priority medications for characterizing developmental changes in drug disposition after extremely preterm birth

Publication Number: 3376.389

Michella Dirani, Universidad San Francisco de Quito, Houston, TX, United States; Matthew Huber, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Nicolas A. Bamat, Children's Hospital of Philadelphia, Swarthmore, PA, United States; Tamorah Lewis, The Hospital for Sick Children, Toronto, ON, Canada; Cindy Hoi Ting Yeung, Dalhousie University, Halifax, NS, Canada; Rachel G. Greenberg, Duke Clinical Research Institute, Durham, NC, United States; Sarah A. Coggins, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Kelly Wade, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Anna O'Brien, Childrens Hospital of Philadelphia, Philadelphia, PA, United States

Background: Extremely preterm (EP) infants are frequently prescribed drugs lacking population-specific pharmacology, safety, or efficacy data. Medications used frequently and across wide developmental periods are particularly concerning because EP infants have distinct drug disposition physiologies that change dynamically after preterm birth. Preventing toxic and ineffective drug exposures would require dosing adjustments with maturation, yet preterm developmental pharmacology research to guide such practices remains limited.

Objective: To help guide preterm developmental pharmacology research priorities, we identified medications that are both frequently used and prescribed across a broad range of postmenstrual (PMA) and postnatal ages (PNA) in EP infants.

Design/Methods: We used data from the Pediatric Health Information System (PHIS) to conduct a retrospective observational cohort study of EP infants admitted by day of life 1 to US children's hospitals between 2015 and 2025. All daily medication prescriptions were identified from birth to discharge or 1 year of age (study period). We first identified all medications prescribed in at least 1% of all study period days across the full cohort. Among these, we defined utilization as the number of prescription days per 1,000 study period days and spread as the interdecile range of PMA and PNA at exposure. We then determined an EP developmental pharmacology priority score by calculating the mean of the z-scores for utilization and spread, for PMA and PNA.

Results: We identified 15,722 EP infants (Table 1). 48 medications were prescribed in > 1% of study period days. The top 20 medications for utilization, spread, and priority for PMA and PNA are displayed in Figures 1 and 2, respectively. The same 20 medications were prioritized when considering PMA vs PNA, with subtle differences in rank order. Caffeine had the highest priority score, driven by very high utilization. Furosemide and lorazepam completed the top 3, with high utilization and spread noted for both. Eight medications prescribed to manage preterm lung disease (caffeine, furosemide, albuterol, ipratropium, budesonide, levalbuterol, chlorothiazide, and sildenafil) and 7 medications prescribed to provide sedation and/or analgesia (lorazepam, methadone, acetaminophen, dexmedetomidine, clonidine, midazolam, and morphine) were among the top 20 priorities.

Conclusion(s): Our findings facilitate the identification of high-priority targets for preterm developmental pharmacology research, highlighting medications for preterm lung disease and sedative/analgesics as particular priorities in this vulnerable population.

Table 1: Cohort Characteristics


Figure 1: Medication utilization rates, PMA spread at prescription and PMA-based priority score in extremely preterm infants hospitalized in US children's hospitals.
Utilization is defined as the number of medication prescription days per 1,000 study period days across the cohort; PMA spread measures the interdecile range for all prescriptions of the medication across the cohort; Priority Score is calculated as the mean of the z-scores for utilization and spread among the 48 medications prescribed in at least 1% of study period days. PMA, postmenstrual age; IDR, interdecile range; US, United States

Figure 2: Medication utilization rates, PNA spread at prescription and PNA-based priority score in extremely preterm infants hospitalized in US children's hospitals.
Utilization is defined as the number of medication prescription days per 1,000 study period days across the cohort; PNA spread measures the interdecile range for all prescriptions of the medication across the cohort; Priority Score is calculated as the mean of the z-scores for utilization and spread among the 48 medications prescribed in at least 1% of study period days. PNA, postnatal age; IDR, interdecile range; US, United States